Field of the Invention
The present invention relates to a method for increasing the expression of SIRT1 mRNA and/or decreasing the expression of SOCS3 mRNA, and especially for regulating the blood glucose level in a subject in need thereof and to a medicament for such treatment, and especially relates to the use of an active component available from an Cistanche tubulosa extract in the treatment of diabetes mellitus.
Description of the Related Art
Diabetes mellitus is a chronic metabolic disorder causes by insufficient insulin secretion or the ineffective use of glucose in the tissue of an organism, which will leads to excessively high level of blood glucose. It is known that insulin is secreted by pancreatic β cells. Insulin is effective in regulating the blood sugar and may stimulate the glucose transport in adipose cells and muscle cells. Obesity, aging and other reasons may cause insufficient insulin secretion or poor insulin sensitivity, resulting in the increase of blood glucose level and diabetes mellitus. Patients of diabetes mellitus may suffer from symptoms such as, laziness, thirst, excessive urination, blurred vision, and weight loss. Long-term high blood sugar levels may lead to the dysfunction and failure of various organs.
Diabetes mellitus can be primarily classified into Type 1 diabetes and Type 2 diabetes. Type 1 diabetes, also known as insulin dependent diabetes mellitus, is caused by an infection or environmental toxins which trigger the patient's own immune system to attack pancreatic β cells. As a result, pancreatic β cells are damaged, resulting in absolute insulin deficiency and causing blood sugar levels to rise. Type I diabetes accounts for approximately 5% to 10% of all patients with diabetes mellitus. Most patients of Type 1 diabetes are diagnosed before the age of 30, and thus Type 1 diabetes is also known as juvenile diabetes mellitus.
Type II diabetes is also known as non-insulin dependent diabetes mellitus. Most patients of Type II diabetes are diagnosed after the age of 40, and thus, it is also known as adult-onset diabetes mellitus. Type II diabetes accounts for approximately 90% to 95% of all patients with diabetes mellitus. Type II diabetes is caused by the resistance to insulin occurring in cells, which gradually decreases the secretion of insulin from pancreatic β cells and causes a diabetic metabolic disorder. Patients of Type II diabetes often simultaneously suffer from hyperlipidemia, obesity and other symptoms. The risk factors of Type II diabetes includes genetic abnormalities, family history of diabetes, age, obesity (especially abdominal obesity), less physical activity, gestational diabetes, and impaired glucose homeostasis, etc.
The prevalence of diabetes mellitus has increased yearly. According to the World Health Organization in 2008, it is expected that in 2030, there will be over 300 million people with diabetes mellitus globally. Currently, the methods used in the clinical treatments of diabetes mellitus including exercise, diet, and drug treatment. Drug treatment includes insulin injection, oral hypoglycemic drugs, such as sulfonylurea drugs (sufonylureas), biguanide drugs (biguanides), α-glucosidase inhibitor, and insulin sensitizers, etc.
The inventors of the present invention found that a compound of formula (I) has an excellent effect on increasing the expression of SIRT1 (sirtuin 1) mRNA and/or decreasing the expression of SOCS3 (suppressor of cytokine signaling 3) mRNA, and is effective in lowering blood glucose, and thus, can be used for regulating the blood glucose level in a subject in need thereof, especially for treating Type I diabetes and/or Type II diabetes in a subject in need thereof:
wherein X is H or C1-C3 alkyl; one of Y and Z is
and the other one is H, OH or
wherein when Y is
Z is
and R1 to R13 are independently H or OH, wherein, R1 to R3 are not simultaneously H, and R8 and R9 are not simultaneously H. Preferably, the compound of formula (I) is at least one of compound (1) and compound (2) as follows and can be obtained from a plant extract, such as a Cistanche tubulosa extract,

Cistanche tubulosa extract belongs to genus Cistanche. The active components of Cistanche tubulosa primarily are phenylethanoid glycosides, including echinacoside, acteoside, and isoacteoside. A research team of Shanghai University of Traditional Chinese Medicine (China) conducted in vitro glucose consumption assay with the use of liver cells and conducted in vivo drug-induced hypoglycemic efficacy trials with the use of mice having type I diabetes or type II diabetes induced by different medicaments. The results showed that acteoside obtained from plantago is effective in promoting the consumption of glucose and can decrease the fasting blood glucose level by enhancing the serum insulin level (see Chinese patent publication no. CN 102283854 A, which is entirely incorporated herein by reference). Therefore, in the present invention, the active ingredients of Cistanche tubulosa extract were determined by using an animal model of diabetes mellitus and a hepatic glucose consumption test.